Abstract
Diabetes-associated cardiac fibrosis is a severe cardiovascular complication. Momordicine I, a bioactive triterpenoid isolated from bitter melon, has been demonstrated to have antidiabetic properties. This study investigated the effects of momordicine I on high-glucose-induced cardiac fibroblast activation. Rat cardiac fibroblasts were cultured in a high-glucose (25 mM) medium in the absence or presence of momordicine I, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed. Increased oxidative stress plays a critical role in the development of high-glucose-induced cardiac fibrosis; we further explored momordicine I's antioxidant activity and its effect on fibroblasts. Our data revealed that a high-glucose condition promoted fibroblast proliferation and collagen synthesis and these effects were abolished by momordicine I (0.3 and 1 μM) pretreatment. Furthermore, the inhibitory effect of momordicine I on high-glucose-induced fibroblast activation may be associated with its activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of reactive oxygen species formation, TGF-β1 production, and Smad2/3 phosphorylation. The addition of brusatol (a selective inhibitor of Nrf2) or Nrf2 siRNA significantly abolished the inhibitory effect of momordicine I on fibroblast activation. Our findings revealed that the antifibrotic effect of momordicine I was mediated, at least partially, by the inhibition of the TGF-β1/Smad pathway, fibroblast proliferation, and collagen synthesis through Nrf2 activation. Thus, this work provides crucial insights into the molecular pathways for the clinical application of momordicine I for treating diabetes-associated cardiac fibrosis.
Original language | English |
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Article number | 3939714 |
Number of pages | 1 |
Journal | Oxidative Medicine and Cellular Longevity |
Volume | 2018 |
DOIs | |
Publication status | Published - Jan 1 2018 |
Keywords
- Animals
- Antioxidants/pharmacology
- Cell Proliferation/drug effects
- Collagen/biosynthesis
- Fibroblasts/drug effects
- Glucose/toxicity
- Models, Biological
- Myocardium/pathology
- NF-E2-Related Factor 2/metabolism
- Phosphorylation/drug effects
- Quassins/pharmacology
- RNA, Small Interfering/metabolism
- Rats, Sprague-Dawley
- Reactive Oxygen Species/metabolism
- Signal Transduction/drug effects
- Smad Proteins/metabolism
- Sterols/chemistry
- Transforming Growth Factor beta1/metabolism
ASJC Scopus subject areas
- Ageing
- Biochemistry
- Cell Biology